WO2004051229A1 - Liquid switch, and microchip and mass-analyzing system using the same - Google Patents
Liquid switch, and microchip and mass-analyzing system using the same Download PDFInfo
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- WO2004051229A1 WO2004051229A1 PCT/JP2003/015416 JP0315416W WO2004051229A1 WO 2004051229 A1 WO2004051229 A1 WO 2004051229A1 JP 0315416 W JP0315416 W JP 0315416W WO 2004051229 A1 WO2004051229 A1 WO 2004051229A1
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- Prior art keywords
- liquid
- flow path
- sample
- switch
- liquid switch
- Prior art date
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0621—Control of the sequence of chambers filled or emptied
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/16—Injection
- G01N30/20—Injection using a sampling valve
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T137/00—Fluid handling
- Y10T137/4891—With holder for solid, flaky or pulverized material to be dissolved or entrained
Definitions
- the present invention relates to a liquid switch for controlling the flow of a liquid, a microphone chip using the same, and a mass spectrometry system.
- microchemical analysis in which chemical operations such as sample pretreatment, reaction, separation, and detection are performed on a microchip, is rapidly developing. According to the microphone mouth chemical analysis, only a small amount of sample is required, and the environmental load is small and highly sensitive analysis is possible.
- Patent Document 1 describes an apparatus that realizes capillary electrophoresis using a microchannel type chip having a configuration in which a groove and a reservoir are provided on a substrate.
- this type of microchip it is important to precisely control the timing at which the sample / buffer is introduced into the flow path in the chip.
- Such techniques are required not only in separation devices and analysis devices, but also in microchemical reaction devices.
- Patent Document 1 Japanese Patent Application Laid-Open No. 2000-200703 Disclosure of Invention
- the present invention has been made in view of the above circumstances, and in a device such as a microchip, the flow of a liquid such as a sample or a buffer is precisely controlled to separate, analyze, or react a sample. It is an object of the present invention to provide a switch structure which can be controlled under desired conditions with good controllability. Another object of the present invention is to provide a switch structure that enables a plurality of processes to be activated at an appropriate timing by capillary force, triggered by one sample injection, without the aid of an external control device. It is in.
- a flow path through which the first liquid passes, a damming portion provided in the flow passage, which dams the first liquid, and a downstream portion of the damming portion, And a trigger flow passage communicating with the flow passage and guiding the second liquid to the damming portion.
- the first liquid is blocked at the blocking section.
- the blocking unit may be configured to absorb and retain the first liquid, or the blocking unit itself exhibits lyophobicity to the first liquid, and the first liquid is provided at the upstream end thereof.
- a configuration in which the body is blocked may be used.
- the liquid sample blocked by the blocking unit flows out downstream of the blocking unit when coming into contact with the second liquid.
- opening of a flow path can be performed with desired controllability at a desired timing by introducing a 2nd liquid, without providing an external control apparatus.
- the damming portion may be configured to include a member that holds the first liquid.
- the second liquid when the second liquid is introduced into the flow path, the liquid surface of the first liquid and the liquid surface of the second liquid held by the member come into contact with each other. Then, the first liquid flows out downstream of the damming portion. In this way, it is possible to open the flow path at a desired timing with good controllability.
- the flow passage surface area per unit volume of the flow passage in the damming portion is larger than the flow passage surface area per unit volume of the flow passage in the other part of the flow passage.
- a structure configured so that This is because a capillary force is generated and a liquid retention effect is exhibited. Specific examples of such a structure include a plurality of particles, a porous body, a structure including a plurality of spaced apart protrusions, and the like.
- the damming portion may be configured to include a region that is lyophobic to the first liquid.
- the lyophobic area is lyophobic to the first liquid It can be obtained by a method in which a flow path is formed using a surface of a substrate having a property and utilizing the surface, or a method in which the surface of the flow path is treated with such a compound.
- a degree of lyophobicity By adjusting the degree of lyophobicity, a smooth transition to the open state and a smooth flow state after the open state can be realized.
- a valve structure may be provided in the trigger passage, and when a predetermined amount of the second liquid is introduced, the valve structure may be operated to close the one trigger passage. By doing so, it is possible to introduce only a predetermined amount of the second liquid.
- the second liquid introduced from the trigger channel is maintained in a band-like form, so that a sample suitable for, for example, separating components can be provided.
- a band-shaped sample suitable for separation operation can be stably introduced. .
- the present invention has a flow path through which a liquid passes, and a damming portion provided in the flow passage to dam the liquid, wherein the damming portion includes a member holding the liquid.
- a liquid switch is provided.
- the switch can be switched to the open state by applying vibration, or by dropping a predetermined liquid substance on the damming portion.
- the member holding the liquid was configured such that the flow path surface area per unit volume of the flow path in the damming portion was larger than the flow path surface area per unit volume of the flow path in the other part of the flow path.
- Structure This is because a capillary force is generated and a liquid retaining action is generated.
- Specific examples of such a structure include a plurality of particles, a porous body, a plurality of protrusions spaced apart, and the like.
- the present invention has a flow path through which a liquid passes, and a damming portion provided in the flow passage to dam the liquid. And a liquid switch comprising a lyophobic surface.
- the switch can be switched to the open state by applying vibration or by dropping a predetermined liquid substance into the damming portion.
- the lyophobic region can be obtained by a method of forming a flow channel using the surface of a substrate that is lyophobic to the above liquid, or by treating the surface of the flow channel with such a compound. .
- a smooth transition to the open state and a smooth flow state after the open state can be realized.
- the moving member further includes a moving member disposed in the flow path to be movable from the damming portion to a position other than the damming portion. It may have a surface that shows lyophilicity for one liquid, so that the position of the moving member can be adjusted from outside the channel.
- the switch when the moving member is outside the region showing the lyophobicity, the switch is in a closed state.
- the moving member is located in the region exhibiting the lyophobicity, the passage along the surface of the moving material becomes the first liquid flow path, and the flow path is opened.
- a position adjusting means for adjusting the position of the moving member from the outside may be further provided, and one of the moving member and the position adjusting means may be a magnet and the other may be a magnetic material. By doing so, the position of the moving member can be adjusted from the outside.
- a flow path through which the first liquid passes a sub flow path communicating with the flow path, a chamber communicating with the sub flow path, a communication path with the chamber, and a second flow path in the chamber
- a trigger flow path for introducing a liquid; and a lyophobic substance showing lyophobicity with respect to the first liquid is stored inside the chamber, and a second liquid is supplied from the trigger flow path.
- a liquid switch is provided, wherein the liquid switch is configured to introduce the lyophobic substance from the chamber to the flow path when introduced.
- the chamber is interposed between a first chamber communicating with the sub-flow path, a second chamber storing the lyophobic substance, and the first and second chambers.
- the second small chamber for storing the lyophobic substance has a structure not communicating with the sub flow path.
- the lyophobic substance may be a liquid or a gas, and may be air or the like.
- the liquid switch is configured such that a lyophobic substance is introduced into a flow path through which the first liquid flows when the second liquid serving as a trigger is introduced, and the flow path is closed.
- a lyophobic substance is introduced into a flow path through which the first liquid flows when the second liquid serving as a trigger is introduced, and the flow path is closed.
- a substrate a sample flow path through which a sample formed on the substrate passes, and a sample separation unit provided in the sample flow path, wherein the sample flow path described above is provided in the sample flow path.
- a microchip is provided, wherein a liquid switch is provided, and the supply of the sample from the sample channel to the sample separation unit is controlled by the liquid switch.
- a substrate a liquid flow path formed on the substrate, through which a liquid passes, and a reaction unit provided in the liquid flow path.
- a microchip is provided, wherein a switch is provided, and supply of liquid from the liquid flow path to the reaction section is controlled by the liquid switch.
- the microchip further includes a reservoir that communicates with the reaction section and into which a reagent is introduced.
- the liquid switch is disposed in a liquid flow path from the reservoir to the reaction section, and the liquid switch is provided from the reservoir.
- the introduction of the reagent into the section may be controlled by the liquid switch.
- the reagent can be, for example, an enzyme digestion solution such as a trypsin digestion solution.
- a substrate a main flow path through which a liquid formed on the substrate passes, a clock flow path that controls a timing at which the liquid passes through a predetermined portion of the main flow path, and a main flow path and a clock
- Microchips are provided. According to the present invention, various processes such as a separation operation and a reaction performed on a chip can be executed with good time controllability by using a clock channel.
- microchips can perform sample separation and reaction under desired conditions with good controllability using a liquid switch.
- liquid mixing, reaction, separation, and the like can be performed at an appropriate timing according to a predetermined schedule.
- a separation means for separating a biological sample according to a molecular size or a property, a pretreatment means for performing a pretreatment including an enzyme digestion treatment on the sample separated by the separation means,
- a mass spectrometry system comprising: drying means for drying the processed sample; and mass spectrometry means for mass analyzing the dried sample, wherein the separation means includes the microchip described above.
- a separation means for separating a biological sample according to a molecular size or a property
- a pretreatment means for performing a pretreatment including an enzyme digestion treatment on the sample separated by the separation means
- a mass spectrometry system comprising: drying means for drying the processed sample; mass spectrometry means for mass analyzing the dried sample; wherein the pretreatment means includes the microchip described above. It is.
- a separation means for separating a biological sample according to a molecular size or a property, a pretreatment means for performing a pretreatment including an enzyme digestion treatment on the sample separated by the separation means, A drying unit for drying the processed sample; and a mass analysis unit for mass analyzing the dried sample, wherein the separation unit, the pretreatment unit, or the drying unit includes the microchip described above.
- the flow of a liquid such as a sample or a buffer is precisely controlled to separate, analyze, or A switch structure for performing a reaction under desired conditions with good controllability is provided.
- FIG. 1 is a diagram illustrating a switch structure according to an embodiment.
- FIG. 2 is a diagram illustrating a structure of a damming portion included in the switch structure according to the embodiment.
- FIG. 3 is a diagram showing a valve structure for holding a trigger liquid in the switch structure according to the embodiment.
- FIG. 4 is a diagram illustrating a switch structure according to the embodiment.
- FIG. 5 is a diagram showing a cross-sectional structure of the switch according to the embodiment.
- FIG. 6 is a diagram showing a structure of the separation device according to the embodiment.
- FIG. 7 is a diagram showing a switch structure according to the embodiment.
- FIG. 8 is a diagram showing a structure of a damming portion included in the switch structure according to the embodiment.
- FIG. 9 is a diagram showing the structure of the microchemical reaction device according to the embodiment.
- FIG. 10 is a diagram showing the structure of the device according to the embodiment.
- FIG. 11 is a diagram showing a switch structure according to the embodiment.
- FIG. 12 is a diagram showing a switch structure according to the embodiment.
- FIG. 13 is a diagram showing a switch structure according to the embodiment.
- FIG. 14 is a diagram showing the structure of the chip according to the embodiment.
- FIG. 15 is a diagram showing a switch structure according to the embodiment.
- FIG. 16 is a schematic diagram showing the configuration of the mass spectrometer.
- Figure 17 is a block diagram of the mass spectrometry system.
- FIG. 18 is a diagram showing a switch structure according to the embodiment.
- FIG. 19 is a diagram showing a switch structure according to the embodiment.
- FIG. 20 is a diagram showing a switch structure according to the embodiment.
- FIG. 21 is a diagram illustrating the structure of the switch according to the embodiment.
- FIG. 22 is a diagram for explaining the operation of the switch according to the embodiment.
- FIG. 23 is a diagram illustrating the structure of the switch according to the embodiment.
- FIG. 24 is a diagram for explaining the operation of the switch according to the embodiment.
- FIG. 25 is a diagram for explaining the operation of the switch according to the embodiment.
- FIG. 26 is a diagram for explaining the operation of the switch according to the embodiment.
- FIG. 27 is a diagram for explaining the operation of the switch according to the embodiment.
- FIG. 27 is a diagram for explaining the operation of the switch according to the embodiment.
- the switch described in each embodiment is used for controlling a liquid moving in a flow path in a microchip having a flow path and a reservoir on a substrate.
- the liquid to be introduced is an aqueous solution unless otherwise specified.
- a quartz substrate is used as a substrate, but a plastic material, silicon, or the like may be used as another substrate material.
- the plastic material include thermoplastic resins such as silicone resin, PMMA (polymethyl methacrylate), PET (polyethylene terephthalate), and PC (polycarbonate), and thermosetting resins such as epoxy resin. . Such a material is easy to mold and can reduce the manufacturing cost.
- a method for forming a portion of the microchip such as a flow path and a reservoir
- a method combining photolithography and etching can be cited, but when a plastic material is used as a substrate material, injection molding, A method such as hot embossing can be adopted.
- FIG. 1 is a top view of the liquid switch.
- FIG. 1 (a) shows the switch in a closed state
- FIGS. 1 (b) and 1 (c) show the switch in an open state.
- a single trigger channel 102 is connected to a side surface of the main channel 101.
- the traveling speed of the liquid in the flow path can be adjusted by appropriately adjusting the degree of hydrophilicity in the flow path, the flow path diameter, and the like. Thereby, the speed of the switch operation can be adjusted.
- a damming portion 105 is provided on the upstream side (left side in the figure) of the area where the main flow path 101 and the trigger flow path 102 intersect.
- the blocking portion 105 is a portion having a stronger capillary force than other portions of the flow path. The following is an example of a specific configuration of the blocking unit 105.
- the flow channel surface area per unit volume of the flow channel in the damming portion 105 is larger than that of the other portion of the flow channel. That is, when the main flow path 101 is filled with liquid, the flow path damming portion 105 is configured to have a larger surface area and a larger solid-liquid interface than the other parts of the flow path. . (i i) Configuration filled with multiple porous bodies and beads
- the surface of the flow passage blocking portion 105 is configured to have a larger surface area and a larger solid-liquid interface than the other portions of the flow passage.
- the columnar body can be formed by an appropriate method according to the type of the substrate.
- a quartz substrate or a quartz substrate it can be formed using a photolithography technique and a dry etching technique.
- a plastic substrate is used, a mold having an inverted pattern of the pattern of the pillar to be formed is manufactured, and molding is performed using the mold to obtain a desired pillar pattern surface.
- a mold is used for photolithography. It can be formed by utilizing the etching technology and the dry etching technology.
- the porous body and beads can be formed by directly filling and adhering them to predetermined locations in the flow channel.
- FIG. 2 is a top view of the blocking unit 105.
- the plurality of pillars 1 2 1 are regularly arranged at substantially equal intervals.
- the area other than the columnar body 1 2 1 is a fine channel 1 2 2.
- the flow channel surface area per unit volume of the flow channel is larger than that of other portions of the flow channel. For this reason, the liquid that has entered the damming portion 105 is retained in the fine channel 122 by capillary force.
- FIG. 1 (a) shows the liquid switch in a standby state.
- the liquid sample 104 introduced into the main flow path 101 is held by the damming portion 105.
- the trigger liquid 106 is introduced at a desired timing from this state, the leading end of the liquid surface of the trigger liquid 106 advances as shown in FIG. 1 (b), and comes into contact with the damming portion 105. Will be done.
- the liquid sample 104 is held in the damming portion 105 by capillary force, but the liquid sample 104 comes into contact with the trigger solution 106 in Fig. 1 (b).
- the liquid sample 104 moves to the right (downstream side) in the figure, and the liquid sample 104 flows out to the downstream side of the main flow path 101 in FIG. 1 (c). That is, the trigger liquid 106 plays a role as priming water, and the operation as a liquid switch is developed.
- the trigger liquid 106 is continuously supplied to the main flow passage 101 when the switch is in the open state.
- control can be reliably performed by using, for example, a valve structure shown in FIG.
- the liquid sample inflow path 130, the diverticule 131, and the liquid sample outflow path 134 are arranged in this order from the upstream side to the downstream side of the flow path. Have been.
- a water-absorbing gel 1 3 2 is arranged in the diverticulum.
- FIG. 3 (b) is a diagram showing a state in which the trigger one solution is introduced into the diverticulum 131, and the volume of the water-absorbing gel 132 is expanded. In this state, the fluid introduced from the upstream side of the liquid sample inflow path 130 can no longer flow out of the diverticule 13 1. That is, the water-absorbing gel 132 functions as a damming member.
- the present embodiment relates to a switch structure using a hydrophobic region as a damming member.
- This liquid switch can be manufactured by forming a groove on the surface of the quartz substrate. Since a quartz substrate is used, the inner wall of the groove has a hydrophilic surface.
- the hydrophobic region can be obtained by subjecting a lid having a quartz glass surface to a hydrophobic treatment.
- this switch is connected to the side of the main flow path 101, which is connected to the flow path 102, and the upstream main flow path 101 of the intersection area.
- a damming section 110 is provided.
- the main flow channel 101 and the trigger flow channel 102 except the damming portion 110 composed of a hydrophobic region are hydrophilic regions.
- the formation of the hydrophilic region and the formation of the hydrophobic region are performed as follows. That is, after providing a covering member for covering the upper surface of the flow channel with respect to the entire flow channel of the main flow channel 101, the sample contact surface of this coating member is made hydrophobic at the damming portion 110. , And the other regions are hydrophilic.
- FIG. 4 (a) The cross-sectional view of the flow channel shown in FIG. 4 (a) illustrates this state.
- the covering member made of quartz glass is used as it is, and in the cross section on the right, the covering member subjected to silazane treatment is arranged with the silazane treated surface inside.
- the liquid surface tip of the liquid sample 104 is made to stay in the area of the damming portion 110 consisting of a hydrophobic area, and the trigger one liquid 106 is formed. It is important to configure the liquid sample 104 to flow smoothly when introduced. In order to realize this, it is desirable to appropriately control the hydrophobicity of the blocking unit 110. As a method of realizing this, for example, there is a method of selecting a material to be subjected to the hydrophobic treatment of the damming portion 110 and optimizing the amount thereof. In addition, by appropriately designing the structure of the flow path, Is also possible.
- FIG. 5 shows an example of such a structure for controlling hydrophobicity.
- FIG. 5 shows an example of such a structure for controlling hydrophobicity.
- FIG. 5 is a cross-sectional view of the dam unit 110 of FIG. 4 (a).
- a plurality of fine flow paths 402 are provided in the substrate 401, and the upper surface thereof is covered with a coating material 403.
- the microchannel 402 has a hydrophilic surface
- the coating material 403 has a hydrophobic surface by silazane treatment.
- the liquid holding power is determined by an appropriate balance between the water holding ability by the capillary force and the hydrophobicity of the flow channel.
- the ratio of the ratio of the hydrophobic surface to the hydrophilic surface can be freely controlled by controlling the number and width of the microchannels 402, and as a result, the desired overall hydrophobicity is obtained. It can be controlled to a value. By controlling such a structure and controlling the surface state, the degree of hydrophobicity can be appropriately controlled.
- Hydrophobic treatment in the present embodiment includes, for example, adhering or bonding a compound having a structure in which a unit that adsorbs or chemically bonds to a substrate material in a molecule and a unit having a hydrophobic decorative group are bonded to the substrate surface. Is realized by: As such a compound, for example, a silane coupling agent or the like can be used.
- silane coupling agent having a hydrophobic group is hexamethine.
- examples include those having a silazane binding group such as rudisilazane, and those having a thiol group such as 3-thiolpropyltriethoxysilane.
- the spin coating method is a method in which a liquid in which a constituent material of a bonding layer, such as a coupling agent, is dissolved or dispersed, is applied all over a spin core. According to this method, the film thickness controllability is improved.
- the spray method is a method of spraying a force coupling agent liquid or the like toward a substrate
- the dipping method is a method of dipping the substrate in a coupling agent liquid or the like. According to these methods, a film can be formed by a simple process without requiring a special device.
- the vapor phase method is a method in which a substrate is heated as necessary, and a vapor such as a cutting agent liquid is caused to flow through the substrate. Even with this method, a thin film can be formed with good film thickness controllability.
- a method of spin-coating a silane coupling agent solution is preferably used. This is because excellent adhesion can be stably obtained.
- the concentration of the silane coupling agent in the solution is preferably 0.01 to 5 v / v%, more preferably 0.05 to 1 v / v%.
- the solvent for the silane coupling agent solution pure water; alcohols such as methanol, ethanol, and isopropyl alcohol; esters such as ethyl acetate, and the like can be used alone or in combination of two or more. Of these, ethanol, methanol and ethyl acetate diluted with pure water are preferred. This is because the effect of improving the adhesion is particularly remarkable.
- the drying temperature is not particularly limited, but is usually in the range of room temperature (25 ° C) to 170.
- the drying time depends on the temperature, but is usually 0.5 to 24 hours. Drying may be performed in air, but may be performed in an inert gas such as nitrogen.
- a nitrogen blow method in which nitrogen is blown onto a substrate while drying is used.
- a silane coupling agent is applied to the entire surface of the substrate by the LB film pulling method.
- a micro-hole pattern having hydrophilic and hydrophobic properties can be formed.
- the hydrophobic treatment can be performed using a printing technique such as a stamp-ink jet.
- the stamp method uses PDMS resin.
- PDMS resin is formed by polymerizing silicone oil to form a resin. Even after resinification, the molecular gap is filled with silicone oil. Therefore, when the PDMS resin is brought into contact with a hydrophilic surface, for example, a glass surface, the contacted part becomes strongly hydrophobic and repels water. Using this to form a recess at the position corresponding to the flow path?
- the DMS block as a stamp and bringing it into contact with a hydrophilic substrate, a flow path by the above-described hydrophobic treatment can be easily manufactured.
- FIG. 6 is a diagram showing an example of a separation device employing a liquid switch for a sample inlet.
- This separation device is a device that moves a sample by utilizing the capillary phenomenon and separates the sample by a separation channel 540 according to the molecular size and the like. There is no need to apply external force such as electric power or pressure, and no driving energy is required.
- This separation device has a configuration in which a separation channel 540 is provided on a substrate 550.
- An air hole 560 is provided at one end of the separation channel 540, and a buffer inlet 510 for injecting a buffer is provided at the other end.
- the separation channel 540 is sealed except for the buffer inlet 510 and the air hole 560.
- the starting portion of the separation channel 540 is connected to a sample quantification tube 530, and the other end of the sample quantification tube 530 is provided with a sample injection port 520.
- the sample quantification tube 5350 is provided with a stop valve 535 at a position just before the intersection with the separation channel 5450.
- the stop valve 5 35 has the same structure as that described in FIG. 3 and the related description.
- FIG. 7 is an enlarged view of the vicinity of the point where the sample quantification tube 530 and the separation channel 540 intersect.
- a liquid switch is formed at this location.
- FIG. 7 is a top view of the liquid switch.
- FIG. 7 (a) shows the switch closed state
- FIGS. 7 (b) and (c) show the switch open state.
- a sample quantification tube 530 is connected to the side surface of the separation channel 540.
- a blocking unit 110 is provided on the upstream side and the downstream side of a region where the separation channel 540 and the sample quantitative tube 530 intersect.
- a separation portion 113 is formed adjacent to the damming portion 110.
- the separation section 113 is filled with silica gel powder for sample separation.
- the silica gel powder is filled into the separation channel 540 by providing a blocking member on the downstream side, and then flowing a mixture of the silica gel powder, the binder, and water into the separation channel 540. Thereafter, the above structure can be obtained by drying and solidifying the mixture.
- a diverticulum 131 is provided in the sample quantitative tube 5330 serving as a trigger channel.
- a water-absorbing gel 1 32 is arranged in the diverticulum 13 1.
- the water-absorbing gel 1332 is preferably made of a water-absorbing polymer or the like that is insoluble in water.
- the water-absorbing gel 1332 is configured to expand in volume when it comes into contact with the inflowing liquid, thereby filling the space of the diverticulum 1331.
- FIG. 8 is a top view of the dam unit 110 of FIG.
- a plurality of hydrophobic regions 191 are regularly arranged at substantially equal intervals.
- the surface of the quartz substrate is exposed, and the region is a hydrophilic region 192.
- the hydrophobicity of the damming portion 110 is appropriately controlled.
- FIG. 7 (a) the liquid surface tip of the buffer 111 is kept in the hydrophobic area 105, and when the trigger liquid is introduced, the buffer 111 smoothly moves to the downstream side. Become fluid.
- FIG. 7 (a) shows the liquid switch in a standby state.
- the buffer 111 introduced into the separation channel 540 is blocked in the blocking section 110.
- the sample 1 1 2 serving as the trigger liquid is introduced at the desired timing. Then, as shown in FIG. 7 (b), the tip of the liquid surface of the sample 112 moves forward and comes into contact with the damming portion 110. In the state shown in Fig. 7 (a), the buffer 111 remains in the damming portion 110, but when the buffer 111 comes into contact with the sample 112 as shown in Fig. 7 (b), the buffer 1 1 1 starts to move to the right (downstream) in the figure.
- the water-absorbing gel 1332 expands in volume and covers the diverticulum 1311. As a result, the sample 112 can no longer flow to the downstream side of the diverticulum 13 1. That is, the water-absorbing gel 132 functions as a damming member.
- FIG. 9 is an example of a microchemical reaction device using a liquid switch.
- This device is composed of a flow channel formed on a quartz substrate by dry etching, a reservoir for storing a solution to be reacted, and a reaction chamber.
- the sample and the reagent are mixed according to a preset time schedule, and the reaction proceeds continuously.
- the protein is trypsinized using this apparatus, and MALD I—TOFMS (Matrix-Assisted Laser Deionization-Time of Flight Mass Spectrometer) is used.
- MALD I—TOFMS Microx-Assisted Laser Deionization-Time of Flight Mass Spectrometer
- a channel or the like in the illustrated form is formed on the surface of a quartz substrate.
- This device does not have an external force applying means such as a pump and an electric field, and the liquid proceeds in the flow channel by capillary force.
- the sample 602 containing the protein introduced into the solution mixing device 600 0 4 and a flow path 606 are branched and flow, and one is guided to the reservoir 612 and the other is guided to the switch 608.
- the detailed structure of the switch 608 is the structure shown in FIG. 4, and the main channel 101 in FIG. 4 corresponds to the channel 611 in FIG. 9, and the trigger-one channel 102 in FIG. Correspond to the flow path 606 in FIG. When the inflow of the sample 602 becomes a trigger, the switch 608 is opened.
- the solution tank 610 stores a trypsin digestion solution, and its liquid level is held at a position higher than the liquid level of a flow channel provided in this apparatus.
- the switch 608 When the switch 608 is in the "closed” state, the trypsin digestion solution is retained at this position.
- the flow path is opened, the trypsin digest moves to the downstream side (lower side in the figure) of the flow path 6 11. As a result, the tryptic digest is led to the reservoir 612, where it is mixed with the protein-containing sample 602. This mixed liquid is guided from the reservoir 612 to the chamber 616 via the flow path 614.
- a chamber 63.0 having an opening is provided at the end of the flow path 606.
- the chamber 6 16 is formed in a large volume and functions as a time delay element. That is, the mixed solution of the protein-containing sample 6.2 and the trypsin digest solution is continuously supplied to the chamber 616 until the chamber is filled, and when the chamber 616 is filled, the mixed solution is supplied. It overflows and moves downstream. Since the switch 608 remains “open”, the trypsin digestion solution is continuously supplied from the solution tank 610, and the sample 602 is also continuously introduced. As a result, the amount of liquid inside the chamber 6 16 gradually increases, and at a certain time, exceeds the capacity and moves downstream. A predetermined time elapses until the chamber 6 16 is filled, during which the protein-containing sample 62 2 is trypsinized at a temperature of 37 ° C. The pH of the solution treated with trypsin is about 7.6.
- the overflowed trypsin treatment liquid branches out into the flow paths 6 18 and 6 20 and flows out.
- the trypsin-treated body guided to the flow path 620 serves as a trigger for the switch 652, so that the switch 608 is opened.
- a chamber 632 having an opening is provided at the end of the flow path 606.
- 6 N—HC 1 is stored in the solution tank 6 24, and its liquid level is held at a position higher than the liquid level of the flow path provided in this device.
- the trypsin treatment is performed on the microchip at the designed evening.
- the reaction time with the trypsin digestion solution can be controlled by adjusting the volume of the chamber 616.
- a plurality of switch structures are provided for an apparatus combining a ultrafiltration apparatus and a separation apparatus.
- sample introduction and flow can be performed automatically. Since a pump for applying an external force and a charge applying means are not required, the entire apparatus can be downsized.
- FIG. 10 is a schematic configuration diagram of an apparatus according to the present embodiment.
- This device consists of an ultrafiltration device 702 and a separation device 704.
- the ultrafiltration device 720 has a first channel 716, a second channel 720, and a switch 712 interposed therebetween as main components.
- the separating device 704 is a device that separates the sample introduced from the switch 726 by the separating unit 730 and collects them from the collecting unit 732.
- Blood introduced from the sample inlet 714 moves through the first channel 716, Via Luta 710, we reach the intersection area of Switch 712.
- the switch 712 is in the “open” state, and the buffer in the buffer tank 706 enters the second flow path 720.
- the buffer moves from the first channel 716 to the downstream side (right side in the figure) together with the plasma that has passed through the outlet 718, and reaches the switch 726 via the channel 724. I do. Some of the samples move to the discharge section 722.
- the switch 726 has the same structure as the structure shown in FIG. When the buffer containing plasma arrives, switch 726 is in the "open" state. Then, as described in the description of FIG. 7, a predetermined amount of the buffer containing the plasma is introduced into the separation unit 730. A stop valve 7500 is provided on the upstream side of the switch 726, so that a buffer containing plasma is prevented from flowing in an excessive amount.
- the developing solution introduced from the buffer tank 728 separates the plasma into a plurality of bands 732 according to the molecular weight. Thereafter, at an appropriate timing, the sample is collected from the collecting section 734, and a component fractionated by molecular weight can be obtained.
- the components recovered in the recovery section 735 are then used for another analysis after a pretreatment and a drying process.
- proteins are identified by MALDI—TOFMS or the like.
- FIG. 11A is a schematic configuration diagram of a switch according to the present embodiment.
- the channel 901 is filled with a buffer 912.
- a trigger channel 902 is provided on a side surface of the channel 901, and a pump 910 is provided in the trigger channel 902.
- the pump 910 includes a water-absorbing region 908, a hydrophobic region 906, and a hydrophilic region 904.
- a buffer is stored in the hydrophilic region 904.
- Specific examples of the water absorbing region 908 include the following. (i) Configuration with multiple pillars
- Air 915 exists in the water absorbing region 908 and the trigger channel 902.
- the pump 910 is provided with an air hole 9505, and is connected to a flow path 9.03 for introducing a trigger liquid (buffer).
- the trigger liquid When the trigger liquid is introduced into the pump 910 via the flow path 903 from the standby state shown in Fig. 11 (a), it leaks into the hydrophobic area 906 and is stored in the hydrophilic area 904
- the buffer is brought into contact with the liquid surface of the hydrophobic region 906.
- the buffer stored in the hydrophilic region 904 moves to the channel 901 side, and is sucked into the columnar body forming region 908 by capillary force.
- the air 915 existing in this area is pushed out into the flow path 901.
- the air 915 plays a role of blocking the flow of the buffer 912 in the flow path 901, and the switch is closed.
- FIG. 12A shows a schematic structure of the switch according to the present embodiment.
- a first trigger one flow path 920 and a second trigger flow path 926 are provided in communication with a side wall of a main flow path 924.
- a hydrophobic region 922 is provided at a position where these flow paths intersect.
- a hydrophobic region 930 is provided in each channel. These hydrophobic regions have a configuration similar to that shown in FIG. 8, and are regions in which circular hydrophobic regions are periodically formed in a predetermined pattern.
- a buffer 927 remains upstream of the hydrophobic area 922 (left side on the paper).
- FIG. 12 (b) shows a state in which the trigger liquid has been introduced into the first trigger channel 920.
- the knocker 9227 and the trigger liquid come into contact, and these form a continuous phase.
- Buffer 9 27 flows on the downstream side in the right direction in the figure Buffer 9 27 flows. That is, the switch is opened.
- the liquid moving in the flow path 1102 is fed back to the switch 1101 on the upstream side via the sub flow path 1100.
- the present invention relates to a switch having a structure that acts by locking and shuts off the flow path 1102.
- This feedback type switch can be effectively used as a switch for stopping the flow of liquid when a specific chamber is filled. For example, when the liquid reaches the point where the sample quantification tube 530 and the separation channel 540 cross each other in the apparatus in the apparatus shown in Fig. 6, it is assumed that further liquid intrusion is suppressed. Is possible.
- Figure 13 (b) shows an example of a mechanism that suppresses changes in flow velocity by such a feedback-type operation.
- a flow path 111 is provided in a substrate 110.
- the upper part of the substrate 110 is a flow path.
- the channel 1 1 1 2 is filled with an inert hydrophobic liquid such as mineral oil.
- a clock line is provided on a microchip, and the flow of liquid in a flow path on the chip is controlled based on the clock line.
- ESI-MS electrospray ionization mass spectrometry
- multiple samples refers to samples obtained by alkylating, enzymatically digesting, and desalting proteins of different types, for example, proteins and peptides contained in spots collected by two-dimensional electrophoresis. .
- FIG. 14 shows the structure of a chip provided with the switch according to the present embodiment.
- FIG. 14 (a) is a top view of the chip.
- a flow path 1203 through which the first processed liquid 1204 passes and a flow path 1203 through which the second processed liquid 1205 passes are formed in parallel.
- a clock channel 1 201 is provided in a direction orthogonal to these. These have a multilayer flow path structure as shown in FIG. 14 (b).
- FIG. 14B is a sectional view of the chip. It has a structure in which a main flow path substrate 122 and a clock flow path substrate 120 are laminated.
- a main flow path 1203 is formed on the surface of the main flow path substrate 1220, and a clock flow path 1201 is formed on the surface of the clock flow path substrate 1210.
- a control flow path 122 The main flow path 1203 is provided with a switch 127.
- the flow of the clock fluid introduced into the clock channel 1 201 is controlled by the time delay chamber 1 202, and then passes through the control channel 1 2 1 2 Then you reach Switch 127. Then, the flow path 123 is opened, and the first treated liquid 1224 moves to the downstream side, and is guided to the ESI-MS injector.
- the clock fluid moves to the downstream side of the clock channel 1221, and after another time delay chamber, reaches the switch 122. Since this switch 122 is a switch of a type in which a flow path is closed when a trigger arrives, a clock fluid serves as a trigger to close the flow path 123. Thereafter, the same applies to the flow path 1203 through which the second treated liquid 1205 passes, and the second treated liquid 1205 moves to the downstream side, and the ESI_MS It is led to the injector.
- FIG. 15 (a) shows the structure of this switch.
- a damming portion 110 made of a hydrophobic region is provided in a main flow path 101, and a liquid sample 104 is dammed in this portion.
- the hydrophilic substrate surface is exposed in portions other than the damming portion 110.
- the structure of the blocking unit 110 is the same as that shown in FIG.
- Figure 18 is an example. This figure is a cross-sectional view of the switch in Fig. 15 (a) viewed from the side. is there. A lid 141 is provided in the flow path 101, and a projection 140 is provided in the lid 141 as vibration applying means. When the protrusion 140 is broken, vibration is applied to the flow path 101 and the switch is opened.
- FIG. 19 and FIG. 20 show another example of a method of starting a switch.
- FIG. 19 the switch is opened by dropping the sample.
- a flow path 159 is formed between the substrate 155 and the lid 156.
- a hydrophobic region 153 is interposed between the water retaining region 152 and the water absorbing region 154.
- An aqueous solution is stored in the water retaining area 152 and an appropriate pressure is applied. Blocked by hydrophobic area 15 3.
- a hydrophilic sample 150 such as blood onto the hydrophobic region 153
- the water retaining region 152 and the water absorbing region 154 continue, and the flow starts from left to right in the figure.
- FIG. 20 shows an example using a moving member.
- a hydrophobic region 153 is interposed between the water retaining region 152 and the water absorbing region 154.
- aqueous solution is stored in the water retention area 152 and is blocked by the hydrophobic area 1553.
- the surface-hydrophilic magnetic material 160 is initially located in the water retention area 152, but it is straddled over the water retention area 152 and water absorption area 154 by externally operating this with a magnet. When it is moved to the position, the water retention area 152 and the water absorption area 154 continue through the hydrophilic surface of the magnetic material 160, and the flow starts from top to bottom in the figure.
- the diameter of the magnetic body 160 is set to be equal to or larger than the width of the hydrophobic region 153. This allows the switch to operate satisfactorily.
- FIG. 16 is a schematic diagram showing the configuration of the mass spectrometer.
- the dried sample is placed on the sample stage. Then, the dried sample is irradiated with a nitrogen gas laser having a wavelength of 337 nm under vacuum. The dried sample then evaporates with the matrix.
- the sample stage is an electrode, and when a voltage is applied, the vaporized sample flies in a vacuum and is detected by a detection unit including a reflector detector, a reflector, and a linear detector.
- FIG. 17 is a block diagram of a mass spectrometry system including the drying device of the present embodiment.
- This system removes some impurities from sample 1001 Perform the following steps: purification 1002, separation 1000 to remove unnecessary components 1003, pretreatment of the separated sample 1005, and drying of the sample after pretreatment 1006.
- Means. Some or all of these means can be mounted on one or more microchips 108. By continuously processing the sample on the microchip 108, it is possible to identify even a small amount of component efficiently and reliably by a method with less loss.
- the damming portion is located at a position close to the trigger channel. Specifically, if the point where the center line of the main flow path and the center line of the trigger flow path intersect is defined as the crossing point, the distance between the intersection and the hydrophobic processing section is 1.5 times or less the width of the trigger flow path. It is preferable that the width be equal to or less than the width of the trigger channel. By doing so, a stable switch operation can be realized.
- the liquid switch can be realized by a flow path pattern drawn with hydrophobic ink without digging a groove for the flow path.
- Figure 21 shows the structure of the chip.
- A is a photograph showing a planar structure
- (B) is a cross-sectional view thereof.
- a hydrophilic slide glass 800 (white polished frost slide glass pre-cleaned, Matsunami Glass Co., Ltd., water contact angle is about 7 degrees) is used as a substrate, and an oil-based pen for glass (YYF 1 , Super stubborn marker one, Zebra Corporation, water contact angle is about 70 degrees, or X100 W—SD, Pentel White, Pentel Corporation, water contact angle is about 10 0 °), a flow path pattern 809 including a 5 mm wide main flow path 805 part, a 1 mm width trigger flow path 806 part, and a hydrophobic processing part 808 was drawn. .
- the flow path was realized by tracing the outer circumference with a pen tip having a width of l mm to 2 mm. Since water is excluded from the hydrophobic region, it flows only between the lines of the flow path pattern 809.
- the hydrophobic processing section 8 08 that stops the liquid in the main flow path 8 05 This was achieved by drawing a line approximately 80 in width with a pen with a sharpened tip.
- a double-sided tape 800 (Niitoms Co., Ltd.) with a thickness of about 0.3 mm is applied, and a cover glass with a hydrophobic surface is placed on top of it. 0.17-0.25 style silicone coated 20X20 marauder, Matsunami Glass Co., Ltd., contact angle with water is about 85 degrees).
- the main flow path 805 and the trigger flow path are formed by the vertical gap 803 with a depth of about 0.3 mm created by this and the horizontal gap sandwiched by the hydrophobic flow path patterns 809. 8 06 is formed.
- FIG. 22 is a series of photographs showing the switching operation of this chip.
- Fig. 22 (A) shows the initial state.
- Figure 22 (B) is a photograph after introducing the black ink 807 (SPS-400 # 1, Platinum Fountain Pen) diluted 10 times from the right end of the main channel.
- the black ink 807 automatically entered the main flow path 805 due to the capillary effect, stopped at the hydrophobic processing section 808, and maintained that state.
- 8 10 (tap water) was introduced.
- Figure 22 (C) is the photograph immediately after.
- the water 810 rapidly enters the trigger channel 806 due to the capillary effect, and at the next moment its liquid level merges with the liquid level of the black ink 807 stopped at the hydrophobic processing section 808.
- the macro-sized main flow path 805 with a width of 5 mm can be opened by the narrower trigger flow path 806. It was shown that this can be achieved simply by drawing a border with hydrophobic ink.
- Example 2 In the present embodiment, the ON operation of the liquid switch was confirmed in a narrower flow path of about 100 / im to about 100. Further, the liquid switch of the present embodiment is a prototype produced by photolithography, which means that a channel system including a large number of liquid switches can be integrated on a chip of several centimeters square.
- FIG. 23 is a plan view showing the structure of a prototype liquid switch. What looks like a T-shape is a groove dug on the silicon substrate 900 by a method described later.
- a main flow path 905 extending to the left and right, a trigger single flow path 906 intersecting at right angles, and a hydrophobic processing section 908 is provided on the right side of the main flow path 905 across the intersection.
- Four types were provided according to the thickness of the channel, the width and location of the hydrophobic treatment section 908, and the direction in which the liquid was introduced into the main channel. Each type is referred to by the alphabetic symbols (A) to (D) attached in Fig. 23.
- a main flow path of 100 m and a trigger flow path of 50 m are provided, and liquid is introduced from the left side opposite to the hydrophobic part 908 as a control (type ( In B), (C), (D), and (E), the liquid is introduced from the right side with the hydrophobic treatment section 908).
- Type (B) has a main flow path of 100 m and a trigger flow path of 50 m, and a hydrophobic part 908 with a width of 5 im, which is partially missing, is provided immediately before the intersection. You. The hydrophobic portion 908 cannot be seen because it is transparent, but is shown by a dotted line in the plan view of FIG.
- Type (C) has a 50 zm main flow path and a 50 m trigger flow path, and has a 5 zm wide hydrophobic part 908 with a partial cut-out just before the intersection.
- Type (D ) Has a main flow path of 100 m and a trigger flow path of 50 m, and a hydrophobic part 908 having a width of 5 m is provided at a position away from the intersection.
- a 1 mm square liquid reservoir was etched at the end of each channel at the same time as the channels.
- Photolithography and channel etching of the channel The entire surface of the clean (110) silicon substrate is thermally oxidized to form a thermal oxide film of 2000 angstroms. Next, a photoresist (S1818, Shi1ey Far East Co., Ltd.) is applied, and a quartz chrome mask on which the flow patterns of the liquid switches of the types (A) to (D) are drawn is used. Exposure and image formation removes the photoresist in the flow path pattern and exposes the oxide film. The exposed oxide film is removed with buffered hydrofluoric acid (16 buffered hydrofluoric acid, Morita Chemical Co., Ltd.) to expose the silicon surface.
- buffered hydrofluoric acid (16 buffered hydrofluoric acid, Morita Chemical Co., Ltd.
- the photoresist remaining on the substrate is completely removed by washing with acetone and ethanol, washed with water and dried, and then etched with 25% TMAH heated to 90 ° C for about 20 minutes.
- TMAH TMAH heated to 90 ° C for about 20 minutes.
- a silicon substrate was obtained in which the flow path pattern portion was etched by about 20 tm. This was immersed in buffered hydrofluoric acid to remove the remaining thermal oxide film.
- the main flow channel 905 and the width of the main flow channel 905 are 100 m on the mask, but widen by about 10% to 20% after etching. The same applies to one trigger channel.
- the surface of the silicon substrate on which the flow path pattern has been etched is hydrophobic, it is immersed in concentrated nitric acid at 90 ° C for 40 minutes to make it hydrophilic. Confirm that the surface of the substrate after washing is hydrophilic, and that the water fills the flow channel by the capillary effect.
- a thin film photoresist (S185, Ship1ey Far East Co., Ltd.) is directly dropped onto the silicon substrate whose surface has become hydrophilic by the chemical oxidation, and spin-coated.
- the alignment is performed, and then exposure and development are performed.
- the hydrophobic processing section 908 exposes the flow channel surface.
- This substrate is placed in a stainless steel container, and silazane is dropped so as not to cover the substrate. Then, the container is sealed and left for one day.
- the vaporized silazane forms a hydrophobic silazane film in the hydrophobic treatment section 908 (this film is resistant to acetone-ethanol washing).
- the thin film photoresist on the substrate was removed with acetone and ethanol, washed with water for at least 10 minutes, and then dried using an air gun. The upper surface of the flow channel was left open without a lid.
- the substrate fabricated by the above method was placed horizontally on the stage of a metallurgical microscope, and this was mounted on a 5 ⁇ or 10 ⁇ objective lens via a CCD attached to the lens barrel. igital H andy cum, Sony).
- the liquid to be introduced into the flow path is a colorless solution obtained by diluting a surfactant (NCW-610A, Wako Pure Chemical Industries, Ltd.) with distilled water by a factor of 100, and a black ink ( Two types of dye solutions were prepared by diluting SPS-400 # 1, Platinum Fountain Pen Co., Ltd. 10 times.
- a dilute surfactant is to avoid the problem that when distilled water is used, the flow rate into the flow channel is extremely slow and the flow channel dries on the way because there is no lid. The reason why the approach speed is slow is probably that the application of the thin film photoresist slightly reduced the hydrophilicity of the substrate surface.
- Fig. 24 is a series of photographs after introducing a colorless solution into the liquid switch (A) from the left side opposite to the hydrophobic processing part 908 (objective lens ⁇ 10). As shown in (1) to (6) in FIG. 24, the colorless solution automatically entered the main flow path 905 and stopped at the hydrophobic processing section 908 after crossing the intersection. From this result, it can be seen that the hydrophobic processing section 908 has an effect of stopping the solution.
- Figure 25 shows a series of photographs after the dye solution was introduced into the main flow channel 905 of the type (B) liquid switch from the right side (objective lens ⁇ 10).
- the main flow stopped at the hydrophobic processing section 908.
- a part of the dye solution passed through the gap between the hydrophobic processing part 908 and the flow path wall and reached the intersection, but did not proceed any further (Fig. 25 (2)).
- a colorless liquid was introduced into the trigger channel 906
- the liquid level merged with the dye liquid level that had stopped earlier (Fig. 25 (3)).
- the dye solution was passed through the main flow channel 905 on the left side of the intersection beyond the hydrophobic processing portion 908.
- Figure 26 shows a series of photographs after the dye solution was introduced into the main channel 905 of the type (C) liquid switch from the right side (5x objective lens).
- the dye solution was stopped at the hydrophobic treatment section 908 (FIG. 26 (1)).
- Trigger When the colorless liquid is supplied from one channel 906, the colorless liquid merges with the liquid surface stopped at the intersection (Fig. 26 (4)), and the merged liquid surface starts moving again. Then, it proceeded to the left side of the main flow passage 905 beyond the intersection of the main flow passage 905. However, in this case, the colorless liquid supplied from the trigger flow path 906 was not the dye liquid that proceeded in the main flow path 905. From this result, it is understood that the switch operation cannot be performed depending on the relationship between the thickness of the main flow path 905 and the thickness of the trigger single flow path 906 and the amount of the supplied liquid.
- Figure 27 shows a series of photographs after the dye was introduced into the main flow channel 905 of the type (D) liquid switch from the right side (5x objective lens). After the dye solution automatically entered the main flow path 905, it stopped at the hydrophobic processing section 908 (FIG. 27 (1)). Next, when a colorless liquid was introduced into the trigger channel 906, the colorless liquid was not sufficiently guided to the hydrophobic treatment section 908, and the switch operation was somewhat unstable (Fig. 27 (2)). .
- the hydrophobic processing section 908 is preferably provided at a location close to the intersection. If the point of intersection of each center line of the main flow path 900 and the trigger flow path 906 is defined as an intersection, the distance between the intersection and the hydrophobic processing section 908 is the width of the trigger flow path 906 The width is preferably 1.5 times or less, and more preferably the width of one trigger channel 906 or less. This makes it possible to realize a stable switch operation.
- the distance is 100 / m, and the width of the trigger channel 906 is about 50 to 60 m.
- the ON operation of the liquid switch can be realized even with a flow path as thin as 1 mm or less, and because it can be manufactured by photolithography technology, it can be integrated, and to realize stable ON operation It is preferable to consider the position of the intersection and the hydrophobic processing part 908, and the surface activity of the solution.
Abstract
Description
Claims
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JP2004556888A JPWO2004051229A1 (en) | 2002-12-02 | 2003-12-02 | Liquid switch and microchip and mass spectrometry system using the same |
US10/537,295 US7274016B2 (en) | 2002-12-02 | 2003-12-02 | Liquid switch, and microchip and mass-analyzing system using the same |
CA 2508456 CA2508456A1 (en) | 2002-12-02 | 2003-12-02 | Liquid switch, and microchip and mass spectrometry system using thereof |
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JP (1) | JPWO2004051229A1 (en) |
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- 2003-12-02 US US10/537,295 patent/US7274016B2/en not_active Expired - Fee Related
- 2003-12-02 CN CNA2003801087746A patent/CN1739016A/en active Pending
- 2003-12-02 CA CA 2508456 patent/CA2508456A1/en not_active Abandoned
- 2003-12-02 WO PCT/JP2003/015416 patent/WO2004051229A1/en active Application Filing
- 2003-12-02 JP JP2004556888A patent/JPWO2004051229A1/en not_active Withdrawn
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WO2005075975A1 (en) * | 2004-02-06 | 2005-08-18 | Nec Corporation | Control structure, separating device, gradient forming device, and micro chip using the same |
WO2006098370A1 (en) * | 2005-03-16 | 2006-09-21 | Nec Corporation | Delay circuit with mechanism for adjusting effective passing time of channel, microchip, and method for fabricating the same |
WO2009130977A1 (en) * | 2008-04-25 | 2009-10-29 | アークレイ株式会社 | Tank for introducing liquid drop thereinto and analyzing device |
JPWO2009130977A1 (en) * | 2008-04-25 | 2011-08-18 | アークレイ株式会社 | Droplet injection tank and analysis tool |
JP5255629B2 (en) * | 2008-04-25 | 2013-08-07 | アークレイ株式会社 | Droplet injection tank and analysis tool |
US8663578B2 (en) | 2008-04-25 | 2014-03-04 | Arkray, Inc. | Tank for introducing liquid drop thereinto and analyzing device |
JP2012532327A (en) * | 2009-07-07 | 2012-12-13 | ベーリンガー インゲルハイム マイクロパーツ ゲゼルシャフト ミット ベシュレンクテル ハフツング | Plasma separation reservoir |
JP2016506509A (en) * | 2012-12-13 | 2016-03-03 | コーニンクレッカ フィリップス エヌ ヴェKoninklijke Philips N.V. | Fluid system with fluid stop |
WO2020144920A1 (en) * | 2019-01-09 | 2020-07-16 | 株式会社フコク | Microchannel chip |
JP2020112383A (en) * | 2019-01-09 | 2020-07-27 | 株式会社フコク | Microchannel chip |
JP7219093B2 (en) | 2019-01-09 | 2023-02-07 | 株式会社フコク | microfluidic chip |
Also Published As
Publication number | Publication date |
---|---|
US20060102836A1 (en) | 2006-05-18 |
CA2508456A1 (en) | 2004-06-17 |
CN1739016A (en) | 2006-02-22 |
US7274016B2 (en) | 2007-09-25 |
JPWO2004051229A1 (en) | 2006-04-06 |
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